MicroRNA-125a-5p is an independent prognostic factor in gastric cancer and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab

Naohiro Nishida, Koshi Mimori, Muller Fabbri, Takehiko Yokobori, Tomoya Sudo, Fumiaki Tanaka, Kohei Shibata, Hideshi Ishii, Yuichiro Doki, Masaki Mori

Research output: Contribution to journalArticle

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Abstract

Purpose: MicroRNA 125a-5p (miR-125a-5p) has been reported to be a tumor suppressor in malignancies of the breast, ovary, lung, and central nervous system. However, the clinical significance of miR-125a-5p in human gastrointestinal cancer has not been explored. We investigated a tumor inhibitory effect of miR-125a-5p in gastric cancer, focusing in particular on the miR-125a-ERBB2 (HER2, HER-2/neu) pathway. Experimental Design: Quantitative RT-PCR was used to evaluate miR-125a-5p expression in 87 gastric cancer cases to determine the clinicopathologic significance of miR-125a-5p expression. The regulation of ERBB2 by miR-125a-5p was examined with precursor miR-125a-transfected cells. Furthermore, we investigated whether miR-125a-5p suppresses proliferation of gastric cancer cells in combination with trastuzumab, a monoclonal antibody against ERBB2. Results: Low expression levels of miR-125a-5p were associated with enhanced malignant potential such as tumor size (P = 0.0068), tumor invasion (P = 0.031), liver metastasis (P = 0.029), and poor prognosis (P = 0.0069). Multivariate analysis indicated that low miR-125a-5p expression was an independent prognostic factor for survival. In vitro assays showed that ERBB2 is a direct target of miR-125a-5p, which potently suppressed the proliferation of gastric cancer cells, and, interestingly, the growth inhibitory effect was enhanced in combination with trastuzumab. Conclusions: miR-125a-5p is a meaningful prognostic marker. Furthermore, miR-125a-5p mimic alone or in combination with trastuzumab could be a novel therapeutic approach against gastric cancer.

Original languageEnglish
Pages (from-to)2725-2733
Number of pages9
JournalClinical Cancer Research
Volume17
Issue number9
DOIs
Publication statusPublished - May 1 2011

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MicroRNAs
Stomach Neoplasms
Neoplasms
Trastuzumab
Gastrointestinal Neoplasms
Ovary
Breast
Research Design
Multivariate Analysis
Central Nervous System
Monoclonal Antibodies
Neoplasm Metastasis
Polymerase Chain Reaction
Lung
Survival
Liver

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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MicroRNA-125a-5p is an independent prognostic factor in gastric cancer and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab. / Nishida, Naohiro; Mimori, Koshi; Fabbri, Muller; Yokobori, Takehiko; Sudo, Tomoya; Tanaka, Fumiaki; Shibata, Kohei; Ishii, Hideshi; Doki, Yuichiro; Mori, Masaki.

In: Clinical Cancer Research, Vol. 17, No. 9, 01.05.2011, p. 2725-2733.

Research output: Contribution to journalArticle

Nishida, Naohiro ; Mimori, Koshi ; Fabbri, Muller ; Yokobori, Takehiko ; Sudo, Tomoya ; Tanaka, Fumiaki ; Shibata, Kohei ; Ishii, Hideshi ; Doki, Yuichiro ; Mori, Masaki. / MicroRNA-125a-5p is an independent prognostic factor in gastric cancer and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 9. pp. 2725-2733.
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T1 - MicroRNA-125a-5p is an independent prognostic factor in gastric cancer and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab

AU - Nishida, Naohiro

AU - Mimori, Koshi

AU - Fabbri, Muller

AU - Yokobori, Takehiko

AU - Sudo, Tomoya

AU - Tanaka, Fumiaki

AU - Shibata, Kohei

AU - Ishii, Hideshi

AU - Doki, Yuichiro

AU - Mori, Masaki

PY - 2011/5/1

Y1 - 2011/5/1

N2 - Purpose: MicroRNA 125a-5p (miR-125a-5p) has been reported to be a tumor suppressor in malignancies of the breast, ovary, lung, and central nervous system. However, the clinical significance of miR-125a-5p in human gastrointestinal cancer has not been explored. We investigated a tumor inhibitory effect of miR-125a-5p in gastric cancer, focusing in particular on the miR-125a-ERBB2 (HER2, HER-2/neu) pathway. Experimental Design: Quantitative RT-PCR was used to evaluate miR-125a-5p expression in 87 gastric cancer cases to determine the clinicopathologic significance of miR-125a-5p expression. The regulation of ERBB2 by miR-125a-5p was examined with precursor miR-125a-transfected cells. Furthermore, we investigated whether miR-125a-5p suppresses proliferation of gastric cancer cells in combination with trastuzumab, a monoclonal antibody against ERBB2. Results: Low expression levels of miR-125a-5p were associated with enhanced malignant potential such as tumor size (P = 0.0068), tumor invasion (P = 0.031), liver metastasis (P = 0.029), and poor prognosis (P = 0.0069). Multivariate analysis indicated that low miR-125a-5p expression was an independent prognostic factor for survival. In vitro assays showed that ERBB2 is a direct target of miR-125a-5p, which potently suppressed the proliferation of gastric cancer cells, and, interestingly, the growth inhibitory effect was enhanced in combination with trastuzumab. Conclusions: miR-125a-5p is a meaningful prognostic marker. Furthermore, miR-125a-5p mimic alone or in combination with trastuzumab could be a novel therapeutic approach against gastric cancer.

AB - Purpose: MicroRNA 125a-5p (miR-125a-5p) has been reported to be a tumor suppressor in malignancies of the breast, ovary, lung, and central nervous system. However, the clinical significance of miR-125a-5p in human gastrointestinal cancer has not been explored. We investigated a tumor inhibitory effect of miR-125a-5p in gastric cancer, focusing in particular on the miR-125a-ERBB2 (HER2, HER-2/neu) pathway. Experimental Design: Quantitative RT-PCR was used to evaluate miR-125a-5p expression in 87 gastric cancer cases to determine the clinicopathologic significance of miR-125a-5p expression. The regulation of ERBB2 by miR-125a-5p was examined with precursor miR-125a-transfected cells. Furthermore, we investigated whether miR-125a-5p suppresses proliferation of gastric cancer cells in combination with trastuzumab, a monoclonal antibody against ERBB2. Results: Low expression levels of miR-125a-5p were associated with enhanced malignant potential such as tumor size (P = 0.0068), tumor invasion (P = 0.031), liver metastasis (P = 0.029), and poor prognosis (P = 0.0069). Multivariate analysis indicated that low miR-125a-5p expression was an independent prognostic factor for survival. In vitro assays showed that ERBB2 is a direct target of miR-125a-5p, which potently suppressed the proliferation of gastric cancer cells, and, interestingly, the growth inhibitory effect was enhanced in combination with trastuzumab. Conclusions: miR-125a-5p is a meaningful prognostic marker. Furthermore, miR-125a-5p mimic alone or in combination with trastuzumab could be a novel therapeutic approach against gastric cancer.

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U2 - 10.1158/1078-0432.CCR-10-2132

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